Bruton tyrosine kinase is a member of the Tec family of non-receptor tyrosine kinases. It consists of a PH domain, a TH domain, a SH3 domain, a SH2 domain, and a catalytic domain. Btk is involved in a variety of signaling pathways, plays an important role in regulation of cell proliferation, differentiation and apoptosis. In addition, Btk is a key signal kinase expressed in all hematopoietic cell types except T lymphocytes and natural killer cells. Moreover, Btk plays a critical role in B cell signaling pathways that stimulate cell-surface B-cell receptor (BCR) stimulation to downstream intracellular responses.
Btk is a key regulator of B-cell development, activation, signaling, arid survival (Kurosaki, Curr Op Imm, 2000, 276-281; Schaeffer and Schwartzberg, Curr Op Imm, 2000, 282-288). In addition, Btk plays a role in a number of other hematopoetic cell signaling pathways, such as Toll like receptor (TLR) and cytokine receptor-mediated TNF-a production in macrophages, IgE receptor (FcεRI) signaling in Mast cells, inhibition of Fas/APO-1 apoptotic signaling in B-lineage lymphoid cells and collagen-stimulated platelet aggregation. See, e.g., C. A. Jeffries, et al., (2003), Journal of Biological Chemistry 278: 26258-26264; Vassilev et al. (1999), Journal of Biological Chemistry 274(3): 1646-1656; and Quek et al. (1998), Current Biology 8(20): 1137-1140.